We are searching for the underlying mechanisms that are responsible for the development of the genomic instability. Replication errors in Genomic instability is a general and characteristic feature of both cancer and aging. DNA, telomeric shortening, increased local DNA damage formation, and localized DNA repair defects, are all possible pathways that can lead to genomic instability. Recently, we have found situations where the genomic instability correlated with a deficiency in DNA repair. We have studied the role of the aging gene, p21 on the DNA repair process. Both p21 and its C-terminal region inhibit DNA repair synthesis activity, while the N-terminal region does not. The addition of p21 antibodies alleviates this inhibition, indicating the effect is specific to p21. Addition of excess PCNA also alleviates this inhibition, suggesting that the inhibition of repair activity by p21 (and its C-terminal fragment) is mediated through its interaction with PCNA. We have studied the molecular interaction of the p53 tumor suppressor gene with damaged DNA. In the course of those studies, we detect a substantial unwinding activity of p53 which is currently under investigation